Acyl modifications in bovine, porcine, and equine ghrelins

Takanori Ida; Hatsumi Tominaga; Eri Iwamoto; Akito Kurogi; Ayaka Okura; Kengo Shimada; Johji Kato; Atsutoshi Kuwano; Hirotaka Ode; Sayaka Nagata; Kazuo Kitamura; Takashi Yazawa; Miho Sato-Hashimoto; Masahiro Yasuda; Mikiya Miyazato; Yuki Shiimura; Takahiro Sato; Masayasu Kojima

doi:10.3389/fendo.2024.1411483

Acyl modifications in bovine, porcine, and equine ghrelins

Front Endocrinol (Lausanne). 2024 May 17:15:1411483. doi: 10.3389/fendo.2024.1411483. eCollection 2024.

Authors

Takanori Ida¹, Hatsumi Tominaga², Eri Iwamoto³, Akito Kurogi¹, Ayaka Okura¹, Kengo Shimada¹, Johji Kato¹, Atsutoshi Kuwano⁴, Hirotaka Ode⁵, Sayaka Nagata⁶, Kazuo Kitamura⁷, Takashi Yazawa⁸, Miho Sato-Hashimoto⁹, Masahiro Yasuda¹⁰, Mikiya Miyazato¹, Yuki Shiimura¹¹, Takahiro Sato¹¹, Masayasu Kojima¹¹

Affiliations

¹ Division for Identification and Analysis of Bioactive Peptides, Department of Bioactive Peptides, Frontier Science Research Center, University of Miyazaki, Miyazaki, Japan.
² Miyazaki Prefecture Industrial Technology Center, Miyazaki, Japan.
³ Clinical Research Center, Kurume University Hospital, Fukuoka, Japan.
⁴ Equine Research Institute, Japan Racing Association, Tochigi, Japan.
⁵ Racehorse Clinic, Ritto Training Center, Japan Racing Association, Shiga, Japan.
⁶ Department of Food Science and Technology, Faculty of Health and Nutrition, Minami Kyushu University, Miyazaki, Japan.
⁷ Department of Projects Research, Frontier Science Research Center, University of Miyazaki, Miyazaki, Japan.
⁸ Department of Biochemistry, Asahikawa Medical University, Hokkaido, Japan.
⁹ Department of Animal Pharmaceutical Science, School of Pharmaceutical Sciences, Kyusyu University of Medical Science, Miyazaki, Japan.
¹⁰ Laboratory of Veterinary Anatomy, Faculty of Agriculture, University of Miyazaki, Miyazaki, Japan.
¹¹ Molecular Genetics, Institute of Life Sciences, Kurume University, Fukuoka, Japan.

Abstract

Ghrelin is a peptide hormone with various important physiological functions. The unique feature of ghrelin is its serine 3 acyl-modification, which is essential for ghrelin activity. The major form of ghrelin is modified with n-octanoic acid (C8:0) by ghrelin O-acyltransferase. Various acyl modifications have been reported in different species. However, the underlying mechanism by which ghrelin is modified with various fatty acids remains to be elucidated. Herein, we report the purification of bovine, porcine, and equine ghrelins. The major active form of bovine ghrelin was a 27-amino acid peptide with an n-octanoyl (C8:0) modification at Ser3. The major active form of porcine and equine ghrelin was a 28-amino acid peptide. However, porcine ghrelin was modified with n-octanol (C8:0), whereas equine ghrelin was modified with n-butanol (C4:0) at Ser3. This study indicates the existence of structural divergence in ghrelin and suggests that it is necessary to measure the minor and major forms of ghrelin to fully understand its physiology.

Keywords: GHS-R; acyl-modification; ghrelin; n-butanoic acid; n-octanoic acid.

MeSH terms

Acylation
Amino Acid Sequence
Animals
Caprylates / metabolism
Cattle
Ghrelin* / chemistry
Ghrelin* / metabolism
Horses
Swine

Substances

Ghrelin
octanoic acid
Caprylates

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported in a part by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan to TI (21K05958) and Takeda Science Foundation to MK.